Benign Mimics Research Articles

Esophageal ulcer associated with inappropriately taken doxycycline: A benign mimicker of esophageal cancer.

Esophageal ulcer associated with inappropriately taken doxycycline: A benign mimicker of esophageal cancer.

Role of p16, Ki67 and CK17 in differentiating benign lesions, cervical intraepithelial neoplasia(CIN) and atypical immature squamous metaplasia(AIM) of uterine cervix

Cervical intraepithelial neoplasia (CIN) is a premalignant lesion capable of progressing to cervical cancer. Despite the existing well-defined criteria, the histopathological diagnosis is subject to high rates of discordance among pathologists. Aim: To study the role of p16, Ki67 and CK17 in differentiating benign lesions, cervical intraepithelial lesions(CIN) and atypical immature squamous metaplasia (AIM)and to improve intra and interobserver reproducibility of diagnosis of cervical neoplasia. Material and Methods: In a cross sectional study, a total of 75 cervical biopsies including benign lesions (n=24), AIM (n=28), CIN (n=23) were studied and analyzed immunohistochemically using p16, Ki67 and CK17 immunomarkers. Data was evaluated using chi-square test. Results: p16 and Ki 67positivity were observed in 91.3% and 78.26% of CIN and 28.57% of AIM respectively. None of the benign lesions expressed p16 and Ki67while CK17 positivity was observed in 46.42% of CIN and 100% of AIM with 12.5% of benign lesions. Conclusion: The three biomarkers (p16, CK17 and Ki67) had a high degree of sensitivity and specificity and appear to be a useful and reliable diagnostic adjunct to improve the routine diagnosis and reduce interobserver variability in cervical biopsy specimens. Immunohistochemical markers such as p16 alone or with Ki67 represents important tool for the pathologists in distinguishing high grade cervical dysplasia from its benign mimics such as AIM and reactive inflammatory lesion thus avoiding overtreatment. Cervical intraepithelial neoplasia (CIN) is a premalignant lesion capable of progressing to cervical cancer. Despite the existing well-defined criteria, the histopathological diagnosis is subject to high rates of discordance among pathologists. Aim: To study the role of p16, Ki67 and CK17 in differentiating benign lesions, cervical intraepithelial lesions(CIN) and atypical immature squamous metaplasia (AIM)and to improve intra and interobserver reproducibility of diagnosis of cervical neoplasia. Material and Methods: In a cross sectional study, a total of 75 cervical biopsies including benign lesions (n=24), AIM (n=28), CIN (n=23) were studied and analyzed immunohistochemically using p16, Ki67 and CK17 immunomarkers. Data was evaluated using chi-square test. Results: p16 and Ki 67positivity were observed in 91.3% and 78.26% of CIN and 28.57% of AIM respectively. None of the benign lesions expressed p16 and Ki67while CK17 positivity was observed in 46.42% of CIN and 100% of AIM with 12.5% of benign lesions. Conclusion: The three biomarkers (p16, CK17 and Ki67) had a high degree of sensitivity and specificity and appear to be a useful and reliable diagnostic adjunct to improve the routine diagnosis and reduce interobserver variability in cervical biopsy specimens. Immunohistochemical markers such as p16 alone or with Ki67 represents important tool for the pathologists in distinguishing high grade cervical dysplasia from its benign mimics such as AIM and reactive inflammatory lesion thus avoiding overtreatment. Normal 0 false false false EN-IN X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:Table Normal; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0cm; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:Calibri,sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:Times New Roman; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;}

Abstract WMP113: Headache At Stroke Onset Is Present In Half Of All Older Children With Arterial Ischemic Stroke

Introduction: Headache at stroke onset occurs in up to a quarter of adults and is associated with younger age, female gender, right hemisphere and cerebellar infarcts. Little is known about headache at stroke onset in children. Methods: Children (29 days-18 years) with clinical and radiographic confirmation of arterial ischemic stroke were prospectively enrolled in the International Pediatric Stroke Study from 2003-2014. Details regarding demographics, stroke presentation and infarct location were obtained from the multi-center, pediatric stroke registry. Headache at stroke presentation was classified and annotated in the registry by the individual site investigators as present, absent or unclear. Results: We analyzed 2103 children. Half of all subjects ≥ 6 yo reported headache at stroke onset (N=509/1047, 49%; Figure). Headache was less prevalent in children < 6 yo (N=112/1056, 11%; p<0.001), though headache presentation was more commonly classified as unclear (10% vs 32%; p<0.001). In children ≥ 6 yo, headache was significantly associated with papilledema (p = 0.03) and vertigo (p = 0.01), but not with hemiparesis (p = 0.11), visual field deficit (p = 0.90), aphasia (p = 0.35), dysarthria (p = 0.44), or ataxia (p = 0.50). Headache was more common in posterior than anterior circulation infarcts (p<0.001). There was a significant association between headache and right or bilateral hemisphere infarcts (p = 0.04) but not with gender (p = 0.76). Conclusion: Headache is more prevalent in children than adults at stroke ictus and shares similar associations, including infarcts involving the posterior circulation and right hemisphere. Headache may be under-reported in young infants and children due to pre-verbal stages of development. These findings have implications for early identification and treatment of pediatric stroke and warrant further investigation in prospective studies to distinguish stroke from more common benign mimics, including migraine.

Benign breast lesions that mimic malignancy

Many benign and reactive lesions of the breast show morphological overlap with malignant lesions. These benign mimics of malignancy often present diagnostic challenges to even the most experienced pathologists. This review focuses on several benign lesions of the breast that mimic malignant entities. For each of these lesions, we describe the key morphological and immunohistochemical features, potential diagnostic pitfalls, and our approach to arriving at the correct diagnosis.

New and Emerging Diagnostic and Prognostic Immunohistochemical Biomarkers in Prostate Pathology.

The diagnosis of minimal prostatic adenocarcinoma can be challenging on prostate needle biopsy, and immunohistochemistry may be used to support the diagnosis of cancer. The International Society of Urologic Pathology currently recommends the use of the basal cell markers high-molecular-weight cytokeraratin and p63, and α-methylacyl-coenzyme-A racemase. However, there are caveats associated with the interpretation of these markers, particularly with benign mimickers. Another issue is that of early detection of presence and progression of disease and prediction of recurrence after clinical intervention. There remains a lack of reliable biomarkers to accurately predict low-risk cancer and avoid over treatment. As such, aggressive forms of prostate cancer may be missed and indolent disease may be subjected to unnecessary radical therapy. New biomarker discovery promises to improve early detection and prognosis and to provide targets for therapeutic interventions. In this review, we present the emerging immunohistochemical biomarkers of prostate cancer PTEN, ERG, FASN, MAGI-2, and SPINK1, and address their diagnostic and prognostic advantages and limitations.

Challenges of Frozen Section in Thoracic Pathology: Lepidic Lesions, Limited Resections, and Margins.

- The use of frozen section in thoracic pathology includes assessment of peripheral lung lesions with lepidic pattern, with greater emphasis on evaluating lung-sparing resections and margin assessment. - To review pitfalls of frozen section in thoracic pathology; in this setting, reduction of false-positive and false-negative diagnosis in lesion identification and margin assessment is critical. - PubMed search of frozen section lung pathology yielded specific references related to the use of frozen section in the identification of lepidic lesions and the clinical recommendation for margin distance. - Frozen section diagnosis is overall accurate in assessment of lepidic lesions. Pitfalls include rare benign mimickers and more common reactive lesions. Standard approaches to gross assessment and margin measurement require further research with increasing use of lung-sparing resections.

USP6 gene rearrangement in nodular fasciitis and histological mimics.

Nodular fasciitis is known to be a benign mimic of sarcoma, both clinically and histologically. Accurate diagnosis, particularly on small biopsies, remains a challenge, as the morphology can be varied and the immunophenotype is essentially non-specific. Recently, rearrangement of the ubiquitin-specific protease 6 (USP6) gene has been reported as a recurrent and specific finding in nodular fasciitis. The aim of this this study was to evaluate the diagnostic utility of USP6 fluorescence in-situ hybridization (FISH) analysis in a subset of spindle-cell proliferations in which nodular fasciitis enters into the differential diagnosis. A database search was performed at the Middlemore Hospital Histopathology Department. All in-house cases diagnosed between 2002 and March 2014 in which nodular fasciitis was considered as a differential diagnosis were retrospectively identified. Twenty cases were retrieved, reviewed and categorized as 'definite', 'possible' or 'definitely not' nodular fasciitis by consensus morphological opinion of three experienced pathologists. FISH analysis for USP6 rearrangement was performed in each case, with a commercially available break-apart probe. Of seven cases that were morphologically categorized as 'definite' nodular fasciitis, six were FISH-positive and one was FISH-negative. Of four cases categorized as 'possible' nodular fasciitis, one was FISH-positive and three were FISH-negative. Nine cases categorized as 'definitely not' nodular fasciitis were all FISH-negative. In the morphologically definitive cases, FISH analysis for USP6 had a sensitivity of 86% and specificity of 100% for a diagnosis of nodular fasciitis. The positive predictive value was 100%, and the negative predictive value 90%. USP6 FISH is a useful ancillary test in cases where nodular fasciitis is a potential diagnostic consideration.

Clinicopathological and immunohistochemical characterization of papillary proliferation of the endometrium: A single institutional experience.

Papillary proliferation of the endometrium is an unusual lesion that is composed of papillae with fibrovascular stromal cores covered with benign-appearing glandular epithelium. We studied the clinicopathological and immunohistochemical features of four cases of endometrial papillary proliferations. All patients were postmenopausal. Two lesions were incidental findings in hysterectomy specimens, and two lesions were detected in endometrial curettage specimens. Based on the degree of architectural complexity and extent of proliferation, we classified papillary proliferations histopathologically into “simple” or “complex” growth patterns. Three cases were classified as simple papillary proliferation, and one case was classified as complex papillary proliferation. Simple papillary proliferations were characterized by slender papillae with delicate stromal cores. In contrast, complex papillary proliferations had intracystic papillary projections and cellular clusters with frequent branching and occasional cytological atypia. All cases showed coexistent metaplastic epithelial changes, including mucinous metaplasia, eosinophilic cell change, and ciliated cell metaplasia. One patient with simple papillary proliferations had coexistent well-differentiated endometrioid carcinoma. One patient had subsequent hyperplasia without atypia, and another patient had subsequent atypical hyperplasia/endometrioid intraepithelial neoplasia; both patients underwent total hysterectomy within four months. Our observations are consistent with previous data demonstrating that endometrial papillary proliferations coexist with or develop into atypical hyperplasia/endometrioid intraepithelial neoplasia or endometrioid carcinoma. It is very important for pathologists to discriminate papillary proliferations from neoplastic lesions (including atypical hyperplasia/endometrioid intraepithelial neoplasia and well-differentiated endometrioid carcinoma) and benign mimickers (including papillary syncytial metaplasia).

Colorectal cancer mimics: a review of the usual suspects with pathology correlation.

Colorectal cancer is the third most commonly diagnosed cancer in men and second most commonly diagnosed cancer in women worldwide. Initial diagnosis of colorectal malignancy is generally made on colonoscopy, sigmoidoscopy or digital rectal examination; however, with increased use of CT as primary investigation in patients with lower gastrointestinal symptoms, the diagnosis of colon cancer is often first apparent to a radiologist prior to more invasive tests. CT can demonstrate a discrete soft-tissue mass that narrows the colonic lumen or focal nodular wall thickening/stricture and a variety of pericolonic changes. Pattern of wall thickening has been described as an aid to differential diagnosis; however, significant overlap remains between primary colonic tumor and non-colonic tumors or benign conditions. Imaging is non-specific, and appropriate clinical history, direct inspection, histological analysis, and sometimes discussion at MDT are essential for accurate diagnosis and treatment planning. In this article, we will review the imaging features of some of these benign and malignant mimics of colorectal cancer, with accompanying histology slides where appropriate.

Fine‐needle aspiration of soft tissue perineurioma: A comparative analysis of cytomorphology and immunohistochemistry with benign and malignant mimics

Soft tissue perineurioma (STP) is a benign peripheral nerve sheath tumor demonstrating uniform perineurial cell differentiation. To the authors' knowledge, the cytomorphologic features of STP remain incompletely characterized, and the distinction between STP and its benign (intramuscular/cellular myxoma) and malignant (low-grade fibromyxoid sarcoma [LGFMS]) mimics is challenging. Fine-needle aspiration (FNA)/core needle biopsies of 25 low-grade myxoid spindle cell neoplasm cases including STP (5 cases), intramuscular/cellular myxoma (16 cases), and LGFMS (4 cases) were reviewed retrospectively for cytomorphologic and immunophenotypic comparison. FNA smears of STP were hypocellular with scattered clusters of spindle cells with bland, slender nuclei; bipolar cytoplasmic processes; and scant myxoid to collagenous matrix. STP commonly lacked the abundant granular myxoid matrix material present in intramuscular/cellular myxoma (20% in STP vs 75% in intramuscular/cellular myxoma; P <.05), but these tumors were otherwise remarkably found to be similar on FNA smears. All STP and intramuscular/cellular myxoma cases lacked cytologic atypia, whereas 50% of LGFMS cases demonstrated mild nuclear atypia. EMA was positive in all STPs, but also was found to be at least focally positive in 60% of intramuscular/cellular myxoma cases (9 of 15 cases) and 75% of LGFMS cases (3 of 4 cases). MUC4 was found to be negative in all 15 intramuscular/cellular myxoma and 5 STP cases, but was positive in all 4 LGFMS cases. STP, intramuscular/cellular myxoma, and LGFMS have significant cytomorphologic overlap. Immunohistochemical staining with EMA is not beneficial due to a lack of specificity. Negative MUC4 staining reliably excludes LGFMS. Therefore, a clinically meaningful approach to the FNA biopsy evaluation of a low-grade myxoid spindle cell neoplasm is to provide a differential diagnosis and to exclude a low-grade sarcoma. Cancer Cytopathol 2016;124:651-8. © 2016 American Cancer Society.

Adaptable texture-based segmentation by variance and intensity for automatic detection of semitranslucent and pink blush areas in basal cell carcinoma.

Pink blush is a common feature in basal cell carcinoma (BCC). A related feature, semitranslucency, appears as smooth pink or orange regions resembling skin color. We introduce an automatic method for detection of these features based on smoothness and brightness. We also introduce a neighborhood correction method for texture area correction. Smoothness and brightness were analyzed over four bands: luminance, red, green, and blue, then merged using variance-based dynamic thresholding. Dermoscopic images of 100 biopsy-proven BCCs and 254 competitive benign mimics were used to train the algorithm. Sixteen color and texture features were extracted from the automatically detected areas. The confusion matrix for the algorithm showed 15 classification errors in the training set for the 354 images: three errors in the BCC set and 12 errors in the benign set. Logistic regression analysis on a separate 1024-image test set was able to achieve good separation of BCC from benign lesions with an area under the receiver operating characteristic curve (ROC) of 0.878 and 0.877 using manually-created and automatically-generated BCC border masks, respectively. This pilot study indicates that automatic detection of semitranslucent and pink blush areas in BCC is feasible using colors and first-order texture statistics.

Lack of ERG-antibody in Benign Mimickers of Prostate Cancer.

Prostate carcinoma (PC) is the second most diagnosed cancer in men worldwide. Prostate tissue in needle biopsy expresses a wide variety of architectural patterns some of which are difficult to interpret. Immunohistochemical markers, such as AMACR, p63 and 34βE12 that are currently used in diagnosing prostate cancer, are of great value, but often their interpretation is ambiguous. In 2005 Tomlins et al. identified an emerging marker, erythroblastosis E26 rearrangement gene (ERG), which is a member of the family of genes encoding erythroblast-transformation specific transcription factors (ETS) with frequent expression in PC. The aim of this study was to investigate the expression of ERG in benign mimickers of PC in needle biopsies and its diagnostic value alone and in combination with AMACK and 34βE12. Of the selected 46 biopsies, two were eventually diagnosed as PC Gleason score 6 as they were simultaneously ERG and AMACR-positive and 34βE12-negative. One case was considered atypical. The remaining 43 biopsies were diagnosed as benign cases: simple atrophy in 13 cases, partial atrophy in 11, adenosis in 9, basal cell hyperplasia in 3, post-atrophic hyperplasia in 3, clear cell hyperplasia in 2 and sclerotic adenosis in 2 cases. None of the 43 benign cores showed evidence of ERG expression. ERG could be preferably used in diagnosing prostate needle biopsies, lesions that are hard to interpret and controversial expression of AMACR/34βE12.

Benign mimics of cervical cancers

Journal of Diagnostic Pathology is a peer reviewed journal published biannually by the College of Pathologists of Sri Lanka. The journal publishes manuscripts dealing with all aspects of pathology. The aim of the journal is to update knowledge and encourage original research in the field of pathology.

Immunohistochemical expression of Ets-related gene-transcriptional factor in adenocarcinoma prostate and its correlation with Gleason score.

Prostate carcinoma is the second leading cause of cancer-related deaths in males worldwide. The burden is expected to grow 1.7 million new cases and 499,000 new deaths by 2030. In developing countries such as India, prostate carcinoma will show an increase by 140% in the next few years. Although the diagnosis of prostate carcinoma can usually be made on histological features, now a days many immunohistochemical (IHC) markers are used to distinguish it from benign mimickers as well as in predicting prognosis and treatment. Out of these markers, Ets-related gene (ERG product) is a proto-oncogene which participates in chromosomal translocations and is frequently over expressed in prostate carcinoma which harbors ERG-transmembrane protease, serine 2 fusion. Fifty cases of carcinoma prostate diagnosed in needle biopsies and prostatic chips, in the Department of Pathology of a tertiary care teaching hospital in Punjab, India, were included in the present study. The slides were observed under the light microscope, and Gleason scoring was done using the 2005 International Society of Urological Pathology modified Gleason system. IHC study for ERG expression was done on all the cases, for which anti-ERG monoclonal rabbit clone antibody EP111 (Dako, Denmark) was used. Lymphocytes and endothelial cells were taken as in built positive controls for staining. The intensity of ERG positivity was scored as no staining (0), weak staining (+1), moderate staining (+2) and intense staining (+3). The H score was then calculated by multiplying the intensity of the stain with the percentage (0-100) of the cells showing that staining intensity. The H-score has a range of 0-300. The relationship between IHC expression and clinico-pathological parameters was compared and analyzed using Chi-square test. P < 0.05 was considered statistically significant. Majority of patients included in the study were in the age group of 61-80 (84% of the total). When ERG expression was studied with age-specific rates, it was not found to be statistically significant. The most common pattern noted in the present study was 4 + 3, constituting 36% of total, followed by 3 + 4 constituting 32%. Calculating the score, the majority of patients had a Gleason score of 5-8, constituting 76% of total. Out of the total fifty cases of prostate carcinoma, ERG was positive in 29 cases (58%) and negative in 21 cases (42%). Fourteen out of 21 (48%) of the ERG positive cases had an intensity score of 3. When the ERG intensity was correlated with the Gleason score group, it was seen that patients having Gleason score 7-8 showed ERG positivity in 19 out of 38 cases (50%), with 11/19 (57%) cases showing an ERG intensity score of 3. The Gleason score group 9-10 showed ERG positivity in 83% (10/12) cases, 20% (2/10) cases showing intensity score of 3. This correlation was found to be statistically significant. ERG immunostaining was performed in a small Indian cohort of prostate cancer patients, diagnosed in trucut biopsy specimens and prostatic chips. ERG expression was found in 58% patients. An increase in the ERG expression was observed with an increase in Gleason score. The intensity of ERG expression, however, decreased with an increasing Gleason score.

Practical issues related to uterine pathology: in situ and invasive cervical glandular lesions and their benign mimics: emphasis on cytology–histology correlation and interpretive pitfalls

In situ and invasive neoplastic glandular lesions of the uterine have cytologic correlates that must be distinguished from a variety of benign and reactive conditions. Careful study of the cytologic features allows discrimination in the majority of cases; however, the designation of ‘atypical glandular cells' is reserved for equivocal cases that cannot be readily resolved. In this article, the cytologic features of endocervical adenocarcinoma in situ and invasive endocervical adenocarcinoma will be presented, highlighting their correlation to the well-known histologic features. Variants of the usual type of endocervical neoplasms that have important clinical and differential diagnostic features, including mucinous adenocarcinoma and clear-cell carcinoma, will be discussed. There are a number of common cytologic mimics of endocervical neoplasms, including tubal metaplasia, directly sampled (abraded) endometrium, and high-grade squamous intraepithelial lesion involving endocervical glands. The cytologic features of these entities and their differentiation from endocervical neoplasia will be explored. Finally, the role of ancillary studies such as human papillomavirus testing in the management of glandular lesions of the cervix will be integrated into the discussion.

Nodular Hidradenoma: A Rare Cytological Diagnosis

Nodular hidradenoma or clear cell hidradenoma are tumors of sweat gland usually seen in 20-50 years age group with female preponderance. We report a case of 45 year old female who came for FNA with a clinical suspicion of sebaceous cyst. Cytosmears showed fairly cohesive groups of uniform, oval to polygonal cells some of which showed cytoplasmic clearing. The cells were lying in a mucoid background along with good number of cyst macrophages. Cytological impression was benign adnexal tumor possibly cystic eccrine hidradenoma which was confirmed on histology as nodular hidradenoma. Cytohistological correlation readily allows differentiation of this unusual neoplasm from other benign and malignant mimics of skin tumours. The prognosis is excellent following excision.

ERG Expression in Prostate Needle Biopsy: Potential Diagnostic and Prognostic Implications.

To investigate the prognostic and diagnostic value of ERG immunohistochemistry (IHC) in prostate needle biopsy when combined with AMACR-CK5/6. ERG IHC was assessed in 119 consecutive prostate needle biopsies where the dual-stain AMACR-CK5/6 IHC was ordered and in 16 cases with a Gleason score (GS) ≥7. IHC results were evaluated in prostate carcinoma (PCA), high-grade prostatic intraepithelial neoplasia (HGPIN), HGPIN with adjacent atypical glands (PINATYP), atypical/suspicious (ASAP) foci, and benign PCA mimickers. GS, HGPIN, extraprostatic extension, perineural invasion, bilateralism of PCA, largest percent of core, and the overall percent of tissue involved by PCA were recorded. ERG was detected in 36% of PCA, 27% of HGPIN, 13% of ATYP/PINATYP, and none of benign mimickers. ERG-positive HGPIN was strongly associated with ERG-positive PCA in the same core compared with ERG-negative HGPIN (P<0.0001). Positive ERG expression in PCA was inversely related to GS and showed trends toward association with higher volume and bilateral disease. ERG was more specific for PCA than AMACR (0.87 vs. 0.23), but less sensitive (0.36 vs. 0.95). In conclusion, ERG IHC is of limited additional diagnostic value when added to AMACR and CK5/6. ERG expression is inversely related to GS and is associated with bilateral involvement and higher PCA tumor volume. ERG-positive HGPIN is strongly associated with the presence of PCA in the same core. Studies investigating the prognostic value of ERG in HGPIN should be implemented to address whether patients with ERG-positive HGPIN are at increased risk for subsequent PCA development.

THE VALUE OF TOX AS A DIAGNOSTIC MARKER FOR MYCOSIS FUNGOIDES (MF)

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL). Differentiation of MF from its benign mimickers is important to ensure proper management. TOX is a critical regulator of early T-cell development that is considered as a useful marker for MF diagnosis and prognosis. The current study aimed to test the role of TOX immunohistochemistry (IHC) as a diagnostic marker of MF differentiating it from its benign mimickers. Materials and Methods: This work was carried out on 103 skin biopsies, 51 MF cases and 52 inflammatory mimickers. The diagnoses were established after clinicopathologic correlation. IHC was done in MF cases for TOX, CD4, CD8 and CD7 (in TOX negative cases), while the other mimickers stained only by TOX. Results: TOX expression showed a significant positive expression in MF cases compared to inflammatory dermatoses, with 62% sensitivity and 100% specificity. There was positive correlation between TOX staining and CD4/CD8 ratio in MF cases. In addition, TOX positivity in plaque MF was stronger than in patch MF. Also, TOX negative MF cases were negative for CD7. Conclusions: Positive TOX expression favors MF, but its negativity doesn't exclude the diagnosis of MF. Combining TOX with CD4/CD8 ratio and CD7 may be useful in diagnosis of MF beside the clinical and histopathological diagnosis. The stronger TOX positivity in plaque more than patch MF may correlate with the progression of the disease. Key Words: TOX, mycosis fungoides, cutaneous T cell lymphoma, marker.

The Use of Transcriptional Profiling to Improve Personalized Diagnosis and Management of Cutaneous T-cell Lymphoma (CTCL).

Although many patients with mycosis fungoides presenting with stage I disease enjoy an indolent disease course and normal life expectancy, about 15% to 20% of them progress to higher stages and most ultimately succumb to their disease. Currently, it is not possible to predict which patients will progress and which patients will have a stable disease. Previously, we conducted microarray analyses with RT-PCR validation of gene expression in biopsy specimens from 60 patients with stage I-IV cutaneous T-cell lymphoma (CTCL), identified three distinct clusters based upon transcription profile, and correlated our molecular findings with 6 years of clinical follow-up. We test by RT-PCR within our prediction model the expression of about 240 genes that were previously reported to play an important role in CTCL carcinogenesis. We further extend the clinical follow-up of our patients to 11 years. We compare the expression of selected genes between mycosis fungoides/Sézary syndrome and benign inflammatory dermatoses that often mimic this cancer. Our findings demonstrate that 52 of the about 240 genes can be classified into cluster 1-3 expression patterns and such expression is consistent with their suggested biologic roles. Moreover, we determined that 17 genes (CCL18, CCL26, FYB, T3JAM, MMP12, LEF1, LCK, ITK, GNLY, IL2RA, IL26, IL22, CCR4, GTSF1, SYCP1, STAT5A, and TOX) are able to both identify patients who are at risk of progression and also distinguish mycosis fungoides/Sézary syndrome from benign mimickers. This study, combined with other gene expression analyses, prepares the foundation for the development of personalized molecular approach toward diagnosis and treatment of CTCL.

Risk stratification by p16 immunostaining of CIN1 biopsies: a retrospective study of patients from the quadrivalent HPV vaccine trials.

Previous studies of p16 immunohistochemistry (IHC) on CIN1 have suggested the likely utility of p16 in stratification of women at risk for subsequent CIN2/3. But those studies had limitations in statistical power, histologic diagnosis, and disease ascertainment. We conducted a retrospective study of p16 IHC on adjudicated CIN1 tissue diagnosed in young women participating in the placebo arm of the quadrivalent human papillomavirus (HPV) vaccine trials. Tissue sections were stained with p16 IHC and hematoxylin and eosin. p16 IHC was scored using LAST criteria, and hematoxylin and eosin-stained sections were reviewed for concordance with the adjudicated diagnosis. p16 IHC, antecedent high-grade cytology, review diagnosis, and HPV16 detection were assessed as independent risk factors for subsequent CIN2/3. Five hundred twenty-four patients with CIN1 biopsies and complete data were identified, 63 (12.0%) of whom developed CIN2/3 in follow-up. p16 positivity (P=0.06), review diagnosis of CIN2/3 (P=0.04), HPV16 positivity (P=0.01), and antecedent high-grade cytology (P=0.02) were (marginally) associated with CIN2/3. In a logistic regression model, the associations with CIN2/3 (vs. other), expressed as odds ratios (95% confidence intervals), were 1.6 (0.91-2.8) for p16, 2.0 (1.0-3.7) for HPV16, and 2.2 (1.1-2.4) for antecedent high-grade cytology. The mean risks for CIN2/3 estimated from the model ranged from 7.6% for negative for all markers to 36.3% for positive for all 3 markers. p16 IHC does not risk stratify CIN1 patients in a manner that would alter recommended management for CIN1. This reinforces the LAST recommendations that p16 should only be used selectively for problematic scenarios, such as CIN2 because of its inherent lack of reproducibility, cases in which one is struggling between CIN1 and CIN2, and benign mimics of CIN3.